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  • Kaseb, Ahmed Omar  (6)
  • Morris, Jeffrey  (6)
  • Qayyum, Aliya  (6)
  • 1
    Online Resource
    Online Resource
    Molecular profiling by circulating tumor DNA (ctDNA) and benefit from anti-PD-1 in HCC.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e15679-e15679
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e15679-e15679
    Abstract: e15679 Background: Molecular profiling has defined actionable mutations in HCC, and has the potential to be used for selection of targeted therapies, as well as for the characterization of predictive biomarkers from approved treatments. Noninvasive strategies are critical to HCC given the challenge of obtaining liver biopsies. We investigated whether profiling by ctDNA could provide predictive and/or prognostic information for HCC patients (pt) treated with immune checkpoint inhibitors. Methods: We analyzed blood samples from 22 HCC pt who underwent treatment with anti-PD-1 using comprehensive genomic testing of ctDNA with a commercially-available platform (Guardant Health, CA). Demographic and treatment data were retrospectively collected with the goal of correlating treatment outcomes and drug response (by imaging and/or AFP) with molecular abnormalities. Results: 17/22 (77.3%) were men; median age was 66 years. 21 patients received nivolumab and 1 received pembrolizumab. 9 were HCV positive and 5 were HBV positive. 15/22 patients had 〉 1 alteration identified. The median number of alterations/pt was 3 (range, 1-8). TP53 was the common altered gene (n = 11) followed by CTNBB1 (n = 8) , TERT (n = 5) KRAS (n = 3) , GNAS (n = 2). Mutations were also seen (n = 1) in KIT, PIK3CA, PTEN, EGFR, NTRK, FGFR2 among others. 6 pt (27.3%) had AFP response and 8 (36.4%) achieved disease control 〉 12 weeks. Mutations involving KIT, PIK3CA and PTEN were associated with shorter progression-free (PFS) (p 〈 .001 for all) and overall survival (OS) (p = .028 for all), whereas GNAS mutation was associated with shorter PFS (p = 0.019) but not OS. No differences in OS or PFS was observed for other alterations, including the presence of CTNNB1 mutation. There were no correlations between specific alterations and objective tumor response (either by imaging or AFP). 32% of pt were progression-free at 6 months. Median OS was not reached, and 62% were alive after 1 year. Conclusions: Identifying non-invasive predictive biomarkers of benefit to immunotherapy is a priority in HCC. Our data suggest that specific ctDNA alterations can provide predictive information for survival (OS and PFS) on immune checkpoint inhibitors. Further larger studies are warranted for confirmation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e15679
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    IGF-1 Child-Turcotte-Pugh score as a predictor of overall survival to therapy in CTP-A, BCLC stage C patients with advanced hepatocellular carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 4_suppl ( 2020-02-01), p. 488-488
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 4_suppl ( 2020-02-01), p. 488-488
    Abstract: 488 Background: Child-Turcotte-Pugh (CTP) A is the standard population for active HCC therapy. The IGF-CTP score, comprises levels of type 1 insulin-like growth factor (IGF-1), bilirubin, INR, and albumin, significantly improved the prediction of overall survival (OS) in recently published studies. Our current study aimed to investigate the accuracy of the IGF-CTP score in predicting OS in HCC Child-Pugh A patients (pts) treated with local and/or systemic therapies (tx). The overall hypothesis is that the IGF-CTP score can further distinguish CP-A pts in terms of overall survival, PFS. Methods: Between 2014 and 2018, a total of 274 pts with new advanced HCC BCLC stage who had available baseline plasma IGF-1 level were retrospectively enrolled. Clinicopathologic features and treatment history were collected. We calculated IGF-CTP scores, used Kaplan-Meier method and log rank test to estimate and compare time to event outcomes between subgroups of patients. Results: 198 pts were CTP Class A, 209 patient underwent systemic tx, 65 underwent local tx [see table] ; 161 were re-classified as IGF-CTP-A with a median OS of 16.09 months (95% CI = 13.06 to 23.29 months) (p 〈 0.0001), whereas 37 patients were reclassified as intermediate risk (IGF-CTP-B) and had significantly shorter OS of 10.66 months (95% CI = 5.49 to 26.51) (p 〈 0.0001). Conclusions: The results of this study support our biologically-driven hypothesis that IGF-CTP score is predictive of overall survival to therapy in advanced HCC treated with local and/or systemic therapy. Among HCC pts with CTP-A class, some are reclassified as IGF-CP-B/C and were found to have significantly poorer prognosis in terms of shorter OS. Future validation of the predictive ability of our IGF-1 score may lead to adopting it as a stratification tool in clinical trials as well as to predict HCC outcome and guide therapy decision in routine practice. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.4_suppl.488
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 3
    Online Resource
    Online Resource
    IGF-Child-Turcotte-Pugh score as a predictor of treatment outcome in Child-Pugh A, advanced hepatocellular carcinoma patients undergoing sorafenib therapy.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e16660-e16660
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e16660-e16660
    Abstract: e16660 Background: Sorafenib is the first systemic therapy approved for advanced HCC treatment; with no accurate tool available to help predict survival and treatment outcome and to guide therapy decisions. Our novel blood-based insulin-like growth factor-1 (IGF)-Child-Turcotte-Pugh (CTP) score comprises levels of IGF-1, bilirubin, INR, and albumin. IGF-CP score significantly improved the prediction of HCC survival in our recently published studies. The current prospective study aimed to compare the overall survival (OS) and progression free survival (PFS) of 116 patients with CTP-A HCC treated with sorafenib whose score is reclassified as IGF-A (AA) to that of patients whose score is reclassified as IGF-B/C (AB/AC). Methods: After the approval of the institutional review boards and signing written informed consent, a total of 116 patients with HCC were prospectively enrolled and started on sorafenib and followed until progression or death. We calculated IGF-CTP scores, used Kaplan-Meier method and log rank test to estimate and compare time to event outcomes between subgroups of patients. Results: 116 patients were CTP class A, 87 of the patients with CTP class A were classified as IGF-CTP-A and had median OS of 13.16 ms (95% CI = 12.04 to 22.6 ms), and a median PFS of 5.82 months (ms) (95% CI = 4.34 to 9.14 ms), whereas 29 patients were reclassified as intermediate risk (IGF-CTP-B) and had had a higher risk of death with a shorter OS of 7.6 months (95% CI = 5.23 to 24.47 months) and shorter PFS of 3.49 months (95% CI = 2.53 to 5.26 months). There was higher overall rate of adverse events in the CTP-A patients reclassified as IGF-CTP B than IGF-CTP A especially in grade III-IV adverse events, upper GI Bleeding, lower GI Bleeding, nose bleeding, renal failure, liver failure, encephalopathy, fatigue, weight loss, anorexia, and vomiting. Conclusions: The results of this study support our biologically-driven hypothesis that among HCC patients with CTP-A class treated with sorafenib, those reclassified as IGF-CTP-B/C will have poorer prognosis in terms of shorter OS and PFS. Thus, our study provides an objective non-invasive strategy to better predict the outcome in HCC patients undergoing systemic therapy. Future validation of our IGF-1 score may lead to adopting it as a stratification tool in clinical trials as well as to predict HCC outcome and guide therapy decision in routine practice.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e16660
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 4
    Online Resource
    Online Resource
    Treatment outcome and prognostic indicators in 26 cases of fibrolamellar hepatocellular carcinoma under interferon based therapy.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e16626-e16626
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e16626-e16626
    Abstract: e16626 Background: Fibrolamellar hepatocellular carcinoma (FLHCC) is a variant of HCC that comprises ∼1%–9% of all HCCs, with about 200 annual cases reported globally, most often affects younger patients (10–35 years of age) with no underlying liver disease. There is no current standard of care therapy for unresectable FLHCC. We report an analysis of the treatment outcomes, and prognostic indicators of 26 cases. Methods: We retrospectively collected clinicopathologic and treatment outcome data from 26 FLHCC patients who received interferon alfa-2b (IFN) based therapy. Median overall survival (OS) and PFS were calculated using Kaplan-Meier curves, and survival rates were compared by the log-rank test. Results: 21 patient underwent treatment with continuous infusion (CI) 5-Fluorouracil (FU) at 200 mg/m2/day for 7 days on, 7 days off plus IFN at 4 million units/m2, subQ every other day for 7 days on, 7 days off, 1 patient FU+IFN+bevacizumab and 4 patients had PIAF (cisPlatin+IFN+Adriamycin+FU). Median age was 24 years (15-44), 13 males and 13 females, 8 of the 26 patients died, the median overall survival was 33.9 months (95% CI, 20.9, NA), estimated 3-year survival was 20.2% (95% CI: 4.1%, 98.5%), median follow up time was 13.4 months (95% CI: 9.79, NA) and median progression-free survival was 11.7 months (95% CI: 5.09, NA). The estimated 1-year survival was 47.9% (95% CI: 29.9%, 76.8%). Finally, FU+IFN combination was the most frequently used systemic therapy. 3/26 pts underwent surgical resection following neoadjuvant treatment with interferon based therapy; Interferon based therapy for the 26 patients had limited side effects, with only 3 of the 26 patients discontinued treatment due to grade 3-4 adverse event in the form of mucositis, severe fatigue and/or hematologic toxicity. Conclusions: Our analyses indicate that CI FU + IFN could be an effective treatment for FLHCC, and may have a neoadjuvant role in this disease with 3/26 were resectable following neoadjuvant treatment with interferon based therapy. This regimen can be well tolerated. Unfortunately, nonsurgical options for patients with FLC remain limited with no approved local or systemic therapies. Therefore, future research is needed to identify better multimodality therapies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e16626
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 5
    Online Resource
    Online Resource
    The role of ALBI and IGF-CTP score in refining prognostication of HCC.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e16659-e16659
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e16659-e16659
    Abstract: e16659 Background: Child-Turcotte-Pugh (CTP) score is widely used in the assessment of prognosis of HCC and CTP-A is the standard criterion for active therapy and clinical trials entry. Recently, ALBI and insulin-like growth factor-1 (IGF)-CTP scores have been reported to improve survival prediction over CTP score. However, comparative studies to compare both scores and to integrate IGF into Albi score are lacking. Methods: After institutional board approval, data and samples were prospectively collected. 299 HCC patients who had data to generate both IGF-CPG and Albi index were used. The ALBI index, and IGF score were calculated, Cox proportional hazards models were fitted to evaluation the association between overall survival (OS) and CTP, IGF-CTP, Albi and IGF, albumin, bilirubin. Harrell’s Concordance index (C-index) was calculated to evaluate the ability of the three score system to predict overall survival. And the U-statistics was used to compare the performance of prediction of OS between the score system. Results: OS association with CTP, IGF-CTP and Albi was performed (Table). IGF-CTP B was associated with a higher risk of death than A (HR = 1.6087, 95% CI: 1.2039, 2.1497, p = 0.0013), ALBI grade 2 was also associated with a higher risk of death than 1 (HR = 2.2817, 95% CI: 1.7255, 3.0172, p 〈 0.0001). IGF-1(analyzed as categorical variable) was independently associated with OS after adjusting for the effects of ALBI grade. Which showed IGF-1 ≤26 was significantly associated with poor OS, P = 0.001. Conclusions: Although ALBI grade and IGF-CTP score in this analysis had similar prognostic values in most cases, their benefits might be heterogenous in some specific conditions. We looked into corporation of IGF-1 into ALBI grade, IGF score with cutoff ≤26 which clearly refined OS prediction and better OS stratification of ALBI-grade.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e16659
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 6
    Online Resource
    Online Resource
    Clinical and prognostic significance of serum levels of fatty acid binding proteins in hepatocellular carcinoma (HCC).
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 4099-4099
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 4099-4099
    Abstract: 4099 Background: Limited data are available about the prognostic effect of fatty acid binding proteins (FABP) in viral and non-viral-related hepatocellular carcinoma (HCC). Previous studies suggested that selected FABP could be a potential target markers for HCC chemotherapy response and may correlated with presence of cirrhosis and poor outcome. We aimed to test the association between plasma levels of Liver (L)-FABP, Heart (H)-FABP, and Adipose (A) FABP and HCC. Methods: we enrolled 767 HCC patients from MD Anderson Cancer Center. Under IRB approval, baseline patients’ characteristics were retrieved from medical records and blood samples were collected and tested form plasma levels of L-, A-, H-, FABPs. Descriptive statistics were performed and the median values of FABPs among 200 normal controls (NC) were used as cutoff values of FABPs. Overall survival (OS) was estimated by Kaplan Meier curve and log rank test. Results: FABPs were highly expressed in HCC cases than controls. Mean values (±SE) of AFABP, HFABP, and LFABP were significantly higher in cases [25.6 (.7), 10.8 (.5), and 47.8 (1.9)] than controls [19.1 (.8), 7.7 (2), 22. 9 (.5)] , P 〈 .001. All FABPs were significantly associated with cirrhosis, higher Child Pugh Score (CTP), advanced stage in Barcelona clinic liver cancer stage (BCLC), higher AFP levels, vascular invasion and thrombosis, and tumor nodularity. Median OS (months) (95%CI) were significantly short in patients with higher level of AFABP, HFABP, and LFABP [9.3 (6.8-11.9), 9.4 (6.8-11.9), and 11.1 (8.8-13.3)] as compared to patients with low levels [16.4 (13.8-18.9), 16.4 (14.2-18.6), and 17.9 (14.9-20.9) respectively (P 〈 .01). The significance was observed in non-viral related HCC for LFABP and HFABP, but not AFBABP. Conclusions: To the best of our knowledge, we describe the largest study correlating FABPs levels with clinical and prognostic characteristics of HCC. Higher levels were associated with poor survival. These findings suggest that LFABP and HFABP may be used as potential prognostic biomarkers for non-viral-related HCC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.4099
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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